ZR2 Versus R2 Regimen in the Treatment of Newly Diagnosed Follicular Lymphoma

Summary

Primary Objective: To compare the complete response rate (CR rate) after induction treatment between the ZR2 regimen and the R2 regimen.\<br/\>\<br/\>Secondary Objectives: To compare the objective response rate (ORR) after induction treatment, progression-free survival (PFS), progression of disease within 24 months (POD24) rate, duration of response (DOR), overall survival (OS), treatment-related adverse events (AEs), and patient quality of life between the two groups.\<br/\>\<br/\>Exploratory Objectives: To compare the histological .transformation (HT) rate at disease progression, minimal residual disease (MRD) negativity rate, changes in tumor microenvironment (TME) biomarkers, and the relationship between genetic biomarkers and efficacy/prognosis between the two groups; to further reveal the unique pattern of systemic immune status remodeling by the ZR2 regimen and identify potential efficacy-predictive biomarkers.

Study Nature Interventional study Study Design Prospective, randomized controlled, exploratory, multicenter clinical study Sample Size 100 cases Principal Investigator Professor Zhou Keshu Sponsor The Affiliated Cancer Hospital of Zhengzhou University Treatment Regimens (4 weeks per cycle) ZR2 Group\<br/\>- Induction Treatment (6 cycles): Zebutinib 160mg bid starting from C1D1; Rituximab 375mg/m² on Day 1; Lenalidomide 20mg qd on Days 1-21.\<br/\>- Maintenance Treatment: Rituximab 375mg/m² on Day 1 (once every 8 weeks for 2 years); Lenalidomide ;ZR2 Group\<br/\>- Induction Treatment (6 cycles): Zebutinib 160mg bid starting from C1D1; Rituximab 375mg/m² on Day 1; Lenalidomide 20mg qd on Days 1-21.\<br/\>- Maintenance Treatment: Rituximab 375mg/m² on Day 1 (once every 8 weeks for 2 years); Lenalidomide 10mg qd on Days 1-21 (once every 4 weeks for 12 times).\<br/\>\<br/\>R2 Group\<br/\>- Induction Treatment (6 cycles): Rituximab 375mg/m² on Day 1; Lenalidomide 20mg qd on Days 1-21.\<br/\>- Maintenance Treatment: Rituximab 375mg/m² on Day 1 (once every 8 weeks for 2 years); Lenalidomide 10mg qd on Days 1-21 (once every 4 weeks for 12 times).\<br/\>\<br/\>Note: Patients who achieve PR during the first 6 cycles of induction treatment may receive an additional 3 to 6 cycles of lenalidomide 20mg until CR is achieved; thereafter, during maintenance treatment, lenalidomide 10mg PO qd is administered on Days 1-21 (once every 4 weeks for 12 times).

Study Endpoints:Primary Endpoint: CR rate after induction treatment (assessed by the 2014 Lugano Classification for Non-Hodgkin Lymphomas).\<br/\>\<br/\>Secondary Endpoints: ORR after induction treatment; PFS; POD24 rate; OS; DOR; treatment-related AEs; patient quality of life.\<br/\>\<br/\>Exploratory Endpoints: HT rate at disease progression; MRD negativity rate; changes in TME biomarkers; relationship between genetic biomarkers and efficacy/prognosis.

Follow-up Schedule:All patients will be followed up for 2 years after completing treatment, once every 3 months.

Conditions

• Follicular Lymphomas

Interventions

DRUG

Zanubrutinib+R2

6 cycles (each cycle lasting 4 weeks): From cycle 1 to cycle 6 (daily), patients received 160 mg of Zanubrutinib twice daily by mouth; From cycle 1 to cycle 6 (on the first day), patients received 375 mg/m2 of Rituximab once every 4 weeks by intravenous injection; From cycle 1 to cycle 6, patients received 20 mg of Lenalidomide once daily by mouth from day 1 to day 21 (if the CrCl was less than 60 mL/min in the previous 2 cycles, the dose was reduced to 10 mg; if this dose was tolerated, it was increased to 20 mg in cycles 3 to 6); After 6 cycles, patients who achieved CR or PR continued to receive the following treatment in cycles 7 to 24: From cycle 7 to cycle 24, patients received 375 mg/m2 of Rituximab once every 8 weeks by intravenous injection (i.e., on the first day of every 2 cycles); From cycle 7 to cycle 18, patients received 10 mg of Lenalidomide once daily by mouth from day 1 to day 21.

DRUG

R2

R2, 6 cycles (each 4 weeks as one cycle): During the first 6 cycles (from the 1st day to the 6th week), receive rituximab 375 mg/m2 every 4 weeks by intravenous injection; from the 1st day to the 21st day of the 1st to 6th cycles, receive lenalidomide 20 mg once daily by oral administration (if the CrCl was less than 60 mL/min in the previous 2 cycles, reduce it to 10 mg; if this dose is tolerated, increase it to 20 mg in the 3rd to 6th cycles); After 6 cycles, patients who achieved CR or PR continue to receive the following administration: In the 7th to 24th cycles, receive rituximab 375 mg/m2 every 8 weeks by intravenous injection (i.e., administer every 1st day of every 2 cycles); From the 7th to the 18th cycle, from the 1st day to the 21st day, receive lenalidomide 10 mg once daily by oral administration. Note: Patients who achieved PR within the first 6 cycles can receive an additional 3 to a maximum of 6 cycles of lenalidomide 20 mg until achieving CR.

Sponsors & Collaborators

• KeshuZhou

  lead OTHER_GOV

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2026-03-23

Primary Completion

2030-03-23

Completion

2030-03-23